Compositions and methods of use for therapeutic antibodies

Abstract

The present invention relates to antibodies that specifically bind to the BAFF receptor (BAFFR). The invention more specifically relates to specific antibodies that are BAFFR antagonists with in vivo B cell depleting activity and compositions and methods of use for said antibodies to treat pathological disorders that can be treated by killing or depleting B cells, such as systemic lupus erythematosus or rheumatoid arthritis or other autoimmune diseases or lymphomas, leukemias and myelomas.

The invention claimed is: 
     
       1. A method of treating an autoimmune disease comprising the step of administering to a subject a composition comprising an isolated antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, the sequences of said CDRs are selected from the group comprising:
 a) SEQ ID NOs: 2, 9, 16, 23, 30, and 37, respectively; 
 b) SEQ ID NOs: 3, 10, 17, 24, 31, and 38, respectively; 
 c) SEQ ID NOs: 4, 11, 18, 25, 32, and 39, respectively; 
 d) SEQ ID NOs: 5, 12, 19, 26, 33, and 40, respectively; 
 e) SEQ ID NOs: 6, 13, 20, 27, 34, and 41, respectively; and 
 f) SEQ ID NOs: 7, 14, 21, 28, 35, and 42, respectively; 
 and wherein said antibody or antigen-binding fragment thereof binds BAFF-R. 
 
     
     
       2. The method of  claim 1 , wherein the autoimmune disease is selected from rheumatoid arthritis, systemic lupus erythematosus, Sjogren's Syndrome, multiple sclerosis and pemphigus vulgaris. 
     
     
       3. The method of  claim 1 , wherein the subject is human. 
     
     
       4. The method of  claim 1 , wherein the antibodies or antigen-binding fragments thereof comprise, respectively, a variable heavy chain comprising the sequence of
 a) SEQ ID NO: 51; 
 b) SEQ ID NO:52; 
 c) SEQ ID NO:53; 
 d) SEQ ID NO:54: 
 e) SEQ ID NO:55; or 
 f) SEQ ID NO:56. 
 
     
     
       5. The method of  claim 1 , wherein the antibodies or antigen-binding fragments thereof comprise, respectively, a variable light chain comprising the sequence of:
 a) SEQ ID NO: 44; 
 b) SEQ ID NO:45; 
 c) SEQ ID NO:46; 
 d) SEQ ID NO47: 
 e) SEQ ID NO:48; or 
 f) SEQ ID NO:49.